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Updated: Jan 4, 2026
Multiparametric Tumor Organoid Drug Screening Using Widefield Live-Cell Imaging for Bulk and Single-Organoid Analysis
Published on: December 23, 2022
Patient-derived organoids as a potential model to predict response to PD-1/PD-L1 checkpoint inhibitors
Giosue Scognamiglio1, Annarosaria De Chiara1, Antonina Parafioriti2
1Pathology Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Naples, Italy.
Abstract:
Selection of cancer patients for treatment with immune checkpoint inhibitors remains a challenge due to tumour heterogeneity and variable biomarker detection. PD-L1 expression in 24 surgical chordoma specimen was determined immunohistochemically with antibodies 28-8 and E1L3N. The ability of patient-derived organoids to detect treatment effects of nivolumab was explored by quantitative and qualitative immunofluorescence and FACS analysis. The more sensitive antibody, E1L3N (ROC = 0.896, p = 0.001), was associated with greater tumour diameters (p = 0.014) and detected both tumour cells and infiltrating lymphocytes in 54% of patients, but only 1-15% of their cells. Organoids generated from PD-L1-positive patients contained both tumour cells and PD-1/CD8-positive lymphocytes and responded to nivolumab treatment with marked dose-dependent diameter reductions of up to 50% and increased cell death in both PD-L1-positive and negative organoids. Patient-derived organoids may be valuable to predict individual responses to immunotherapy even in patients with low or no immunohistochemical PD-L1 expression.
Insights
Patient-derived organoids show promise in predicting responses to immune checkpoint inhibitors like nivolumab, even when programmed cell death ligand 1 (PD-L1) expression is low. This approach may overcome challenges in selecting cancer patients for immunotherapy.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Discovery
Background:
- Selecting cancer patients for immune checkpoint inhibitor therapy is difficult due to tumor heterogeneity and inconsistent biomarker detection.
- Programmed cell death ligand 1 (PD-L1) expression is a key biomarker, but its detection can be variable.
Purpose of the Study:
- To evaluate the utility of patient-derived organoids in predicting responses to nivolumab treatment.
- To compare the sensitivity of different antibodies for detecting PD-L1 expression in chordoma specimens.
Main Methods:
- Immunohistochemistry was used to determine PD-L1 expression in 24 chordoma specimens using antibodies 28-8 and E1L3N.
- Patient-derived organoids were analyzed using immunofluorescence and FACS analysis to assess treatment effects.
- Organoids were treated with nivolumab to evaluate dose-dependent responses.
Main Results:
- The E1L3N antibody was more sensitive for PD-L1 detection and correlated with larger tumor diameters.
- PD-L1 expression was detected in tumor cells and infiltrating lymphocytes in 54% of patients.
- Organoids from PD-L1-positive patients responded to nivolumab with significant dose-dependent diameter reduction and increased cell death.
Conclusions:
- Patient-derived organoids can model treatment effects of nivolumab.
- Organoids may predict immunotherapy response in patients with low or undetectable PD-L1 expression.
- Organoid models offer a promising tool for personalized cancer immunotherapy.
